The present study investigates the presence of vitamin D receptor (VDR) in cells of the rat oligodendrocyte (OL) lineage. VDR transcripts were detected by in situ hybridization in a fraction of rat OL in secondary cultures. The VDR protein was shown to be co-localized in cells that are also recognized by an anti-myelin basic protein (MBP) antibody. Likewise, in vivo, VDR-positive cells were found in the brain white matter, such as the internal capsule of the striatum or the corpus callosum but also in the spinal cord. At least part of these positive cells in vivo correspond to OL, since they were co-stained by an anti-carbonic anhydrase II antiserum. Northern blot analyses of the CG-4 OL cell line demonstrated that the VDR transcripts are already found in the O-2A precursors. There was a two-fold increase in the relative abundance of these transcripts in differentiated OL or in type-2 astrocytes. 1, 25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] increased the pool of transcripts encoding its own receptor, the VDR. The hormone also enhanced the abundance of the mRNA of the nerve growth factor (NGF) and of its low-affinity receptor, the p75(NTR) protein. By contrast, the hormone had no effect on the levels of MBP or proteolipid protein (PLP) mRNA. This finding suggests that unlike retinoic acid (RA) or thyroid hormone, 1,25-(OH)(2)D(3) has no regulatory action on the synthesis of myelin proteins.